Low-density compositions and particulates including same

ABSTRACT

The present invention provides low-density compositions, as well as particulates formed, at least in part, from such compositions. Preferred low-density materials include, for example, hollowspheres, low-density minerals, and low-density wood materials (e.g., sawdust). The low-density compositions of the invention can be formed as particulates, or cores, suitable for use in forming enzyme granules, e.g., marums, layered granules, prills, drum granules, agglomerated granules, or the like. Granules are disclosed having advantageous properties, e.g., low dusting, storage stable, fast enzyme-release profile, low true density, etc. The granules of the invention are especially useful, for example, in liquid detergents and cleaners, such as predominantly aqueous, liquid laundry detergents. In one embodiment, granules are provided having a true, or volumetric, density within a range of from about 0.95 to about 1.4 g/cm 3 . The granules can be economically produced in commercial quantities by way of a marumerization, drum granulation, fluid-bed spray-coating, pan-coating, or other suitable process.

This application claims priority to U.S. Provisional Application No.60/115,255, filed Jan. 8, 1999, which is incorporated herein in itsentirety.

FIELD OF THE INVENTION

The present invention relates to low-density compositions, as well asparticulates formed, at least in part, from such compositions. Moreparticularly, the present invention provides low-density compositionsincluding a non-porous or minimally porous, low-density material.Particulates formed from the low-density compositions of the inventionare especially useful as cores for enzyme granules.

BACKGROUND OF THE INVENTION

The use of proteins such as pharmaceutically important proteins, e.g.,hormones, and industrially important proteins, e.g., enzymes, has beenrapidly growing in recent years. Today, for example, enzymes findfrequent use in the starch, dairy, and detergent industries, amongothers.

In the detergent industry, in particular, enzymes are often configuredin a granular form, with an eye toward achieving one or more desirablestorage and/or performance characteristics, depending upon theparticular application at hand. In these regards, the industry hasoffered numerous developments in the granulation and coating of enzymes,several of which are exemplified in the following patents andpublications:

U.S. Pat. No. 4,106,991 describes an improved formulation of enzymegranules by including within the composition undergoing granulation,finely divided cellulose fibers in an amount of 2-40% w/w based on thedry weight of the whole composition. In addition, this patent describesthat waxy substances can be used to coat the particles of the granulate.

U.S. Pat. No. 4,689,297 describes enzyme containing particles whichcomprise a particulate, water dispersible core which is 150-2,000microns in its longest dimension, a uniform layer of enzyme around thecore particle which amounts to 10%-35% by weight of the weight of thecore particle, and a layer of macro-molecular, film-forming, watersoluble or dispersible coating agent uniformly surrounding the enzymelayer wherein the combination of enzyme and coating agent is from 25-55%of the weight of the core particle. The core material described in thispatent includes clay, a sugar crystal enclosed in layers of corn starchwhich is coated with a layer of dextrin, agglomerated potato starch,particulate salt, agglomerated trisodium citrate, pan crystallized NaClflakes, bentonite granules or prills, granules containing bentonite,kaolin and diatomaceous earth or sodium citrate crystals. The filmforming material may be a fatty acid ester, an alkoxylated alcohol, apolyvinyl alcohol or an ethoxylated alkylphenol.

U.S. Pat. No. 4,740,469 describes an enzyme granular compositionconsisting essentially of from 1-35% by weight of an enzyme and from0.5-30% by weight of a synthetic fibrous material having an averagelength of from 100-500 micron and a fineness in the range of from0.05-0.7 denier, with the balance being an extender or filler. Thegranular composition may further comprise a molten waxy material, suchas polyethylene glycol, and optionally a colorant such as titaniumdioxide.

U.S. Pat. No. 5,324,649 describes enzyme-containing granules having acore, an enzyme layer and an outer coating layer. The enzyme layer and,optionally, the core and outer coating layer contain a vinyl polymer.

WO 91/09941 describes an enzyme containing preparation whereby at least50% of the enzymatic activity is present in the preparation as enzymecrystals. The preparation can be either a slurry or a granulate.

WO 97/12958 discloses a microgranular enzyme composition. The granulesare made by fluid-bed agglomeration which results in granules withnumerous carrier or seed particles coated with enzyme and bound togetherby a binder.

Notwithstanding such developments, there is a continuing need for enzymegranules which have additional beneficial or improved characteristics.For example, while enzyme granules for dry (e.g., powdered) detergentformulations have become widely known and extensively developed (asexemplified above), few, if any, granule formulations are availablewhich are suitable for incorporation in liquid detergents.

In some respects, formulators of enzyme granules for liquid detergentsmust address concerns much like those encountered with dry detergentformulations. It should be appreciated, however, that a liquid-detergentenvironment presents a variety of challenges of its own. Some of theseconsiderations are discussed next.

In both liquid and dry detergent formulations, enzyme granules should becapable of providing sufficient enzyme activity in the wash. It is alsogenerally desirable to have granule with a relatively fast releaseprofile. Thus, the enzyme load for each granule needs to be protectedfrom the various harsh components of the liquid formulation (e.g.,peroxygen bleaches, such as sodium perborate or sodium percarbonate, andthe like), yet the means of achieving such protection must not undulyhinder enzyme release. As is well known by those working in the field,it is often problematic to simultaneously provide good protection forthe enzyme and a fast release profile.

Another concern, which is common to most all enzyme granules, relates toattrition resistance. In today's state of ever-increasing environmentalconcern and heightened awareness of industrial hygiene, it is importantto keep enzyme dust within acceptable levels. It should be appreciatedthat human contact with airborne enzyme dust can cause severe allergicreactions. For these reasons, enzyme granule formulators continue theirendeavors to control (reduce) the susceptibility of enzyme granules toattritional breakdown.

With particular regard to liquid detergent formulations, one problemwith the use of particles (which would include enzyme granules) inliquids is that there is a tendency for such products to phase separateas dispersed insoluble solid particulate material drops from suspensionand settles at the bottom of the container holding the liquid detergentproduct. Phase stabilizers such as thickeners or viscosity controlagents can be added to such products to enhance the physical stabilitythereof. Such materials, however, can add cost and bulk to the productwithout contributing to the laundering/cleaning performance of suchdetergent compositions. Further, it is to be noted that the known enzymegranules are generally unsuitable for use in typical liquid detergentsas such granules generally have an unacceptably high density (e.g., 1.45g/cm³, or higher) which would cause them to drop out of suspension in arelativity short period of time (i.e., much less than the typicalproduct shelf life).

A further problem associated with particles in liquids is that it hasbeen observed that the particles can induce visual inhomogeneities inthe final product. This represents a problem, as composition aestheticsis a key element in terms of consumer acceptance.

In view of the above, the development of a low-density,enzyme-containing granule is needed in order to provide cleaning benefitfor liquid detergents. The low density is desired so that the particleswill stay suspended in the detergent throughout the intended lifecycleof the product. Additionally, it is desired to have the enzymesprotected from the harsh detergent environment so that they remainactive throughout the product lifecycle. It is also desirable to have arelatively fast enzyme release profile.

It is therefore an advantage of the present invention to providelow-density particulate compositions and enzyme granules suitable foruse in liquid-detergent or cleaner compositions. Preferred particulatecompositions and granules of the present invention are characterized byone or more of the following desirable features: they have a truedensity less than 1.4 g/cm³; they exhibit sufficient enzyme activity inthe wash; they have a relatively fast enzyme-release profile; they haverelatively low susceptibility to attritional breakdown; they tend toremain dispersed and suspended in the liquid detergent or cleaner duringstorage and use (e.g., for at least 3 weeks, and preferably for at least4 weeks); they have sufficient retained activity in storage; theyprovide an acceptable (pleasing) visual appearance.

The production of such a granule exhibiting two or more of the abovefeatures has been especially challenging to the industry. For example,the industry is in need of enzyme particulates and granules for liquiddetergents that have a low true density (e.g., less than 1.4 g/cm³, andpreferably less than about 1.2 g/cm³), a low susceptibility toattritional breakdown (e.g., no greater than 1.0 ug/g ), and retainedactivity in storage (e.g., greater than 50%). Moreover, an especiallydesirable granule would additionally disintegrate quickly in the washliquor to release its enzyme activity. It is an advantage of the presentinvention to provide granules meeting such specifications.

It is still a further advantage of the present invention to providelow-density enzyme granules that can be made economically and incommercial quantities. To this end, the present invention providesexemplary methods of producing such granules, e.g., by way of amarumerization, drum granulation, fluid-bed spray coating, pan-coatingprocess, or other suitable process.

SUMMARY OF THE INVENTION

One aspect of the present invention provides a low-density compositionincluding a non-porous or minimally porous, low-density material (e.g.,hollowspheres, low-density minerals that are minimally soluble andminimally porous in water, low-density wood materials, or any mixturethereof), a binder or binder system (e.g., sucrose), and one or moreenzymes (e.g., a hydrolytic enzyme, such as a protease, amylase,cellulase, lipase, esterases and/or peptidase).

In one embodiment of the invention, the non-porous or minimally porous,low-density material is comprised of hollowspheres (e.g., borosilicateglass hollowspheres, fused glass hollowspheres, ceramic hollowspheres,plastic hollowspheres, or the like). One particularly preferred type ofhollowsphere is available commercially under the tradename Q-cel, fromPQ Corporation.

Preferably, the low-density composition of the invention has a specificgravity of no greater than about 1.4 g/cm³; and more preferably nogreater than about 1.2 g/cm³ (e.g., within a range of between 0.95 and1.15 g/cm³).

Another aspect of the present invention provides an enzyme-carrying corefor enzyme granules. According to one embodiment, the enzyme-carryingcore comprises (i) a low-density composition including (a) a non-porousor minimally porous, low-density material and (b) a binder or bindersystem; and (ii) an enzyme enrobing said composition.

In one embodiment of the enzyme-carrying core, the non-porous orminimally porous, low-density material is selected from the groupconsisting of hollowspheres, low-density minerals that are minimallysoluble and minimally porous in water, low-density wood materials, andany mixture thereof. According to one preferred embodiment, thenon-porous or minimally porous, low-density material is comprised ofhollowspheres (e.g., Q-cel, from PQ Corporation).

The enzyme-carrying core of the invention can be substantially free ofenzymes therein (i.e., it can be a non-enzyme containing core); or thecore can contain one or more enzymes. In one embodiment, the core is anon-enzyme containing core, which can be coated with one or moreenzymes, as desired.

Preferably, the enzyme-carrying core of the invention has a specificgravity of no greater than about 1.4 g/cm³, and more preferably nogreater than about 1.2 g/cm³ (within a range of between 0.95 and 1.15g/cm³).

In another of its aspects, the present invention provides a low-densityenzyme granule. In one embodiment, the granule comprises: (i) a coreformed of a low-density composition including a non-porous or minimallyporous, low-density material; (ii) one or more enzymes; and (iii) anouter coating.

According to one embodiment, the non-porous or minimally porous,low-density material is selected from the group consisting ofhollowspheres, low-density minerals that are minimally soluble andminimally porous in water, low-density wood materials, and any mixturethereof. In a preferred embodiment, the non-porous or minimally porous,low-density material is comprised of hollowspheres (e.g., borosilicateglass hollowspheres).

Preferably, the granules of the present invention have a specificgravity of less than 1.4 g/cm³. In one embodiment, the granules have aspecific gravity of no greater than about 1.2 g/cm³ (e.g., within arange of between about 0.95 and 1.15 g/cm³).

Still a further aspect of the present invention provides a method formaking a low-density granule. In one embodiment, for example, the methodincludes the steps of:

c) preparing a well-mixed blend of components, including (i) one or moreenzymes, (ii) a non-porous or minimally porous, low-density material,and (iii) a binder; and

d) granulating the blend into discreet particulates.

As an additional step, the method can further involve overcoating theparticulates with a cosmetic coating (e.g., HPMC, PEG, and TiO₂).

In another embodiment, granules of the present invention are formed bycarrying out the steps of:

a) selecting a seed or carrier particle;

b) coating the seed with a low-density composition including anon-porous or minimally porous, low-density material;

c) coating the low density composition with one or more enzymes; and

d) overcoating with a cosmetic coating.

The non-porous or minimally porous, low-density material is preferablyselected from the group consisting of hollowspheres, low-densityminerals that are minimally soluble and minimally porous in water,low-density wood materials, and any mixture thereof. In one preferredembodiment, the low-density material is comprised of hollowspheres(e.g., Q-cel, from PQ Corporation).

These and other features, aspects and advantages of the presentinvention will become apparent from the following detailed descriptionand examples, in conjunction with the appended claims.

DETAILED DESCRIPTION OF THE INVENTION

The present invention provides low-density compositions, as well asparticulates formed, at least in part, from such compositions. Thelow-density compositions of the invention include, at least in part, anon-porous or minimally porous, low-density material. Particulatesformed from the low-density compositions of the invention are especiallyuseful as cores for enzyme granules (e.g., marums, layered granules,prills, drum granules, agglomerated granules, or the like). In thisregard, the compositions can further include one or more proteins, e.g.,hydrolytic enzymes; and/or the compositions, or particulates formedtherefrom, can be enrobed with such proteins. The advantage in using thelow-density material (also referred to as a bulking agent), is thatparticulates, cores and granules with densities much lower than thoseachievable by prior methods can be produced. This can have a bearing ona number of applications, such as dispersion of a suspended particle ina liquid, flotation or buoyancy control of particles in specializedapplications (i.e. chromatographic columns), segregation manipulation inpowder applications, etc.

As used herein, the term “density” refers to “true density,” “specificgravity” or “volumetric density,” as opposed to “bulk density” (unlessotherwise stated). The former can be determined, for example, by volumedisplacement using a liquid in which the particulates or granules do notdissolve (e.g., by way of mineral oil immersion).

Generally, according to one embodiment, a low-density composition of thepresent invention includes a non-porous or minimally porous (e.g., lessthan 0.25 by water vapor porosity test; preferably less than 0.20; mostpreferably less than 0. 10), low-density material, e.g., hollowspheres,low-density minerals, low-density wood materials, or any combinationthereof, and a binder material. Optionally, one or more proteins, suchas an enzyme, can further be included in the low-density composition.The composition can be configured, for example, as a particulate. Wherethe particulates are intended for use in liquid wash solutions, they arepreferably adapted to be readily soluble or dispersable in the washliquor.

In situations where the product desired is a low-density granule, suchparticulates can be used as cores, upon which one or more layers can beapplied. For example, one or more of the following layers can be appliedto a particulate, or core, of the present invention: (i) an enzyme layersurrounding the core (especially where non-enzyme containingparticulates are utilized); (ii) optionally, a barrier layer forguarding the enzyme(s) against potentially inactivating substancesand/or preventing enzyme leakage; and (iii) an outermost layer, e.g., aprotective or aesthetic overcoat. For granules used in detergents, theoutermost layer provides a barrier to the harsh detergent elements aswell as gives the desired aesthetic properties to the granule.

In exemplary granules of the present invention, the non-porous orminimally porous, low-density material amount is preferably about 1-20%(w/w, relative to the weight of the granule); the enzyme amount ispreferably about 0.5-30% (w/w, relative to the weight of the granule);and the outer coating amount is preferably about 1-50% (w/w, relative tothe weight of the granule).

Preferably, the low-density material is non-porous or minimally porousin water, substantially non-reactive, and has a low bulk density (e.g.,less than 1 g/ml, and preferably no greater than 0.6 g/ml). Preferredlow-density materials include, for example, hollowspheres, low-densityminerals that are minimally soluble and minimally porous in water, andlow-density wood materials. Suitable hollowspheres include, for example,borosilicate glass hollowspheres, fused glass hollowspheres, ceramichollowspheres and plastic hollowspheres. One particularly preferred typeof hollowsphere is available commercially under the tradename Q-cel,from PQ Corporation. Exemplary low-density minerals include aluminumpalmitate, aluminum tri-stearate, lithium borohydrate, and potassiumborohydride, among others. Suitable low-density wood materials include,for example, saw dust, such as from balsa wood.

Other, optional, low-density materials that may be included in thelow-density composition include, for example, fumed silica, low densityforms of zeolites (such as used for molecular sieving), low densityforms of silicates (such as sodium aluminosilicates used as flow aidsfor powders), low density forms of silicon dioxide (such as those usedas flow aids for powders), milled corncob, aerogel shards, hollow fibers(e.g., Dacron (DuPont)), among others. As previously mentioned, it ispreferred herein that the low-density composition of the inventionshould include at least one non-porous or minimally porous low-densitymaterial. Thus, if a generally porous low-density material is used, itis preferred that one or more non-porous or minimally porous materialsare also employed.

In one embodiment, the low-density composition of the invention isformed into a particulate, or core, about a small seed or carrierparticle. A seed or carrier particle is an inert particle upon which thelow-density material (along with a binder and, optionally, one orenzymes) can be deposited (e.g., coated, layered, etc.). Suitable seedparticles include inorganic salts, sugars, sugar alcohols, small organicmolecules such as organic acids or salts, minerals such as clays orsilicates or a combination of two or more of these. Suitable solubleingredients for incorporation into seed particles include sodiumchloride, potassium chloride, ammonium sulfate, sodium sulfate, sodiumsesquicarbonate, urea, citric acid, citrate, sorbitol, mannitol, oleate,sucrose, lactose and the like. Soluble ingredients can be combined withdispersible ingredients such as talc, kaolin or bentonite. Seedparticles can be fabricated by a variety of granulation techniquesincluding: crystallization, precipitation, pan-coating, fluid-bedcoating, fluid-bed agglomeration, rotary atomization, extrusion,prilling, spheronization, drum granulation and/or high shearagglomeration. In the particulates of the present invention, if a seedparticle is used, then the ratio of seed particles to particulates is1:1. Similarly, in the granules of the present invention, the ratio ofcores to granules is also 1:1. Preferably, the seed particle deliversacceptable strength while not adversely affecting the density of thefinal core or granule.

Suitable binders, contemplated for use herein, include common yellowdent starch, modified starches (e.g., hydroxypropyl addition,ethoxylation, acetylation, acid thinning etc.), sugars (e.g., sucrose,dextrose, fructose, lactose etc.), maltodextrin, polyvinylpyrolidine(PVP), polyethylene glycol (PEG), xanthum gum, gum arabic, acacia gum,alginate, carageenan, waxes (e.g., carnuba, beeswax, paraffin and blendsthereof), high melting point surfactants (e.g., mp between 40 and 80°C.).

Proteins that are within the scope of the present invention includepharmaceutically important proteins such as hormones or othertherapeutic proteins and industrially important proteins such asenzymes.

Any enzyme or combination of enzymes may be used in the presentinvention. Preferred enzymes include those enzymes capable ofhydrolyzing substrates, e.g. stains. These enzymes, which are known ashydrolases, include, but are not limited to, proteases (bacterial,fungal, acid, neutral or alkaline), amylases (alpha or beta), lipases,cellulases and mixtures thereof Particularly preferred enzymes aresubtilisins and cellulases. Exemplary subtilisins are described in U.S.Pat. No. 4,760,025, EP Pat. No. 130 756 B1 and PCT Application WO91/06637, which are incorporated herein by reference. Exemplarycellulases include Multifect L250™ and Puradax™, commercially availablefrom Genencor International. Other enzymes that can be used in thepresent invention include oxidases, transferases, dehydratases,reductases, hemicellulases and isomerases.

Among the places in the granule where the enzyme can be loaded include:centrally within the low-density material (e.g., in a layer around acentrally located seed particle); intermixed (e.g., homogeneously) withthe low-density material; as a layer over, or surrounding, thelow-density material; as a layer separated from the low-density materialby one or more other layers; as well as any combination thereof.

Suitable plasticizers useful in the present invention include polyolssuch as glycerol, propylene glycol, polyethylene glycol (e.g., low MWPEGS), urea, or other known plasticizers. Suitable anti-agglomerationagents include fine insoluble or sparingly soluble materials such astalc, TiO₂, clays, amorphous silica, magnesium stearate, stearic acidand calcium carbonate. Plasticizers and anti-agglomeration agents can beincluded, for example, in an overcoating applied to a granule.

As previously mentioned, a barrier layer can be used to slow or preventthe diffusion of substances that can adversely affect the protein orenzyme in the granule. The barrier layer can be made up of a barriermaterial and can be coated over the core and/or over an enzyme layerthat surrounds the core; and/or the barrier material can be included inthe core. Suitable barrier materials include, for example, starch,inorganic salts or organic acids or salts. In one embodiment, thebarrier layer comprises starch and a binder (e.g., sucrose) coated overa enzyme-containing or carrying, low-density core.

As noted above, the granules of the present invention can comprise oneor more coating layers. For example, such coating layers may be one ormore intermediate coating layers or such coating layers may be one ormore outside coating layers or a combination thereof. Coating layers mayserve any of a number of functions in a granule composition, dependingon the end use of the enzyme granule. For example, coatings may renderthe enzyme resistant to oxidation by bleach, prevent enzyme leakage,bring about the desirable rates of dissolution upon introduction of thegranule into an aqueous medium, or provide a barrier against ambientmoisture in order to enhance the storage stability of the enzyme andreduce the possibility of microbial growth within the granule.

Suitable coatings include water soluble or water dispersiblefilm-forming polymers such as polyvinyl alcohol (PVA), polyvinylpyrrolidone (PVP), cellulose derivatives such as methylcellulose (MC),hydroxypropyl methylcellulose (HPMC), hydroxyethyl cellulose,carboxymethyl cellulose, hydroxypropyl cellulose, polyethylene glycol,polyethylene oxide, gum arabic, xanthan, carrageenan, chitosan, latexpolymers, and enteric coatings. Furthermore, coating agents may be usedin conjunction with other active agents of the same or differentcategories.

Suitable PVAs for incorporation in the coating layer(s) of the granuleinclude partially hydrolyzed, fully hydrolyzed and intermediatelyhydrolyzed PVAs having low to high degrees of viscosity. Preferably, theouter coating layer comprises partially hydrolyzed PVA having lowviscosity. Other vinyl polymers which may be useful include polyvinylacetate and polyvinyl pyrrolidone. Useful copolymers include, forexample, PVA-methylmethacrylate copolymer and PVP-PVA copolymer andenteric co-polymers such as those sold under the tradename Eudragit®(Rhone Poulenc).

The coating layers of the present invention may further comprise one ormore of the following: plasticizers, extenders, lubricants, pigments,and optionally additional enzymes. Suitable plasticizers useful in thecoating layers of the present invention are plasticizers including, forexample, polyols such as sugars, sugar alcohols, or polyethylene glycols(PEGs), urea, glycol, propylene glycol or other known plasticizers suchas triethyl citrate, dibutyl or dimethyl phthalate or water. Suitablepigments useful in the coating layers,.of the present invention include,but are not limited to, finely divided whiteners such as titaniumdioxide or calcium carbonate or colored pigments and dyes or acombination thereof. Preferably such pigments are low residue pigmentsupon dissolution. Suitable extenders include sugars such as sucrose orstarch hydrolysates such as maltodextrin and corn syrup solids, clayssuch as kaolin and bentonite and talc. Suitable lubricants includenonionic surfactants such as Neodol, tallow alcohols, fatty acids, fattyacid salts such as magnesium stearate and fatty acid esters.

Adjunct ingredients may be added to the enzyme granules of the presentinvention. Adjunct ingredients may include: metallic salts;solubilizers; activators; antioxidants; dyes; inhibitors; binders;fragrances; enzyme protecting agents/scavengers such as ammoniumsulfate, ammonium citrate, urea, guanidine hydrochloride, guanidinecarbonate, guanidine sulfamate, thiourea dioxide, monoethanolamine,diethanolamine, triethanolamine, amino acids such as glycine, sodiumglutamate and the like, proteins such as bovine serum albumin, caseinand the like etc.; surfactants including anionic surfactants, ampholyticsurfactants, nonionic surfactants, cationic surfactants and long-chainfatty acid salts; builders; alkalis or inorganic electrodlytes;bleaching agents; bluing agents and fluorescent dyes and whiteners;enzyme stabilizers such as betaine, peptides and caking inhibitors.

Preferably, the granules produced in accordance with the presentinvention are roughly round, or spherical, in shape.

The true, or volumetric, density of the granules can be measured bymethods well known in the art, such as by volume displacement using aliquid in which the granules do not dissolve (e.g., mineral oilimmersion). Preferably, the granules produced according to the teachingsherein have a true density of less than 1.4 g/cm³; more preferably nogreater than about 1.2 g/cm³. In one embodiment, the granules have adensity of between 0.95-1.4 g/cm³; preferably between about 0.95-1.2g/cm³; and most preferably between about 1-1.15 g/cm³.

The granules of the present invention may be particularly useful inconnection with liquid detergents. In one preferred embodiment, thegranules are dispersed and suspended within a liquid detergent having awater content of greater than 50%, and preferably at least about 60%. Inone embodiment, the granules have a retained activity in storage for 3weeks, at 35° C. in such a liquid detergent of at least 50%, andpreferably at least 60%, and most preferably at least 70% (e.g., 85% orgreater). In another embodiment, the granules have a retained activityin storage for 4 weeks, at 37° C. in such a liquid detergent of at least50%, and preferably at least 60%, and most preferably at least 70%(e.g., 85% or greater). In yet a further embodiment, the granules have aretained activity in storage under ambient, or normal, storageconditions for 6 months in such a liquid detergent of at least 50%, andpreferably at least 60%, and most preferably at least 70% (e.g., 85% orgreater).

The granules described herein may be made by methods known to thoseskilled in the art of particle generation, including but not limited tomarumerization, drum granulation, fluid-bed spray-coating, pan-coating,or other suitable process, or combinations of such techniques. Severalexemplary methods for producing the particulate compositions andgranules of the invention are described next.

In one embodiment, a seed particle is charged into a fluid bed coaterand fluidized. A coating solution consisting of a binder or bindersystem along with a non-porous or minimally porous, low-density material(e.g., hollowspheres) and optionally including other low-densitymaterials is sprayed onto the seed to generate a low densityparticulate, or core. Also, the non-porous or minimally porous,low-density material (and other low-density materials, if applicable)may be added dry along with application of a binder spray in either apan or fluidized bed coater. After the core is generated, an enzyme canbe layered onto the core. Optionally, this may be followed by otherlayers whose purpose can be, for example, buffering, providing aprotective barrier, bulking, providing another value/performance addedmaterial. Finally, a cosmetic coating can be applied to provideaesthetics and protection from the environment. If desired, the entireprocess can be performed in a pan coater. Moreover, any part of thisprocess can be performed in either a pan coater or a fluidized bedcoater.

Suitable seed particles for use in the just-described method include,for example, a sugar crystal, salt crystal, non-pareil, a prill with anacceptable melting point, an extruded particulate, a particulate from adrum granulation, etc.

In another embodiment for forming a granule, a non-porous or minimallyporous, low-density material (e.g., hollowspheres) can be blended in asolution consisting of melted components and little or no water or othersolvent. This solution can be fed to a spinning disc, centrifugal nozzleor any other type of prilling device which is used to generate sphericalparticles of sizes between 50 and 3000 um. The prills are generated atsome height above a collection area which allows them to cool and hardenas they fall. Alternatively, a counter-current chilling air-stream maybe used to facilitate prill hardening and control particle velocities.Optionally, enzyme may be added to the hot-melt solution in the form ofa dry powder, enzyme-crystal slurry or paste, enzyme precipitate slurryor paste or in a solubilized form in either an aqueous or non-aqueoussolvent. In any of the above enzyme additions, solvent of liquid carrierconcentration in the hot-melt cannot rise to above a level wherespheroidal, non-friable prills are no longer formed. These enzyme prillscan then be cosmetically coated, as an option.

In a further embodiment, low-density enzyme granules of the presentinvention are made by an extrusion method by adding the non-porous orminimally porous, low-density material (e.g., hollowspheres) to the dryblend and then processing as described in, for example, U.S. Pat. No.5,739,091, incorporated herein by reference.

In yet another embodiment, low-density enzyme granules of the presentinvention are made by a drum granulation method by adding the non-porousor minimally porous, low-density material (e.g., hollowspheres) to thedry blend and processing as described in, for example, in PCT WO90/09440, incorporated herein by reference.

In still a further embodiment, the non-porous or minimally porous,low-density material (e.g., hollowspheres) can be blended into asolution/slurry that is used to produce the core of a microencapsulatedproduct. This solution can be sprayed along with a shell solutionthrough a binary phase nozzle, where the core solution exits through theinner liquid port and the shell solution exits through the outerconcentric liquid port, and atomized via centrifugal force, mechanicalvibration, jet cutting, sonics, cross shear from a liquid or gas stream,electromagnetic field, etc. Depending on the shell, the microencapsulatecan be collected in a liquid based collection bath, a solid media thatfacilitates free-flow of the product or in static or countercurrent airstream that allows hardening/setting up of the product before it reachesa collection vessel. Optionally, the microencapsulate can be driedand/or cosmetically coated.

The shell can be composed of any material(s) that efficiently entrap theinner core and provide enough rigidity so that the microcapsule can behandled in relevant applications without significantly deforming,agglomerating, decomposing or in other ways becoming non-utile.

It should be noted that technologies such as extrusion and drumgranulation, where a significant compression force is employed in theproduction of a granule, might exclude some low density materials ifthey cannot maintain the low density structure under granulation workingpressure. For these technologies, a low density material with asatisfactory pressure/compression tolerance must be employed.

EXAMPLES

The following examples are representative and not intended to belimiting. One skilled in the art could choose other enzymes, fillers,binders, seed particles, methods and coating agents based on theteachings herein.

Example 1

Pan Coated Cores

50 Kgs of non-pareils sieved to between 35 to 40 standard mesh werecharged into a 350L pan-coater. The pan was rotated and the product washeated to approximately 50° C. Approximately 1535 grams of sucrosesyrup, 62.5% w/w, was sprayed onto the non-pareils until they weresufficiently wet. 432 grams of borosilicate hollowspheres (Q-cel 6042S,produced by PQ Corporation) were added to the pan and dispersedthroughout the non-pareils. The pan was allowed to rotate until thenon-pareils were sufficiently dry. This method of ingredient additionand drying was repeated 40 more times. After 41 additions, the particleswere split into two equivalent coating pans.

To each pan, 1535 grams of sucrose syrup was sprayed. Subsequently, 640grams of hollowspheres were added. This method of addition was performed18 times in each pan. Subsequently, 23 more hollowsphere additions weredone in each pan by spraying 1535 grams of sucrose syrup and adding 768grams of hollowspheres for each addition.

After all of the hollowsphere additions were complete, 3 additions of ashellac solution (confectioners glaze) were applied which totaled 2% wlwof the final product.

These low density cores were harvested and classified to between 14 to25 standard mesh. The final harvest weight was 232 Kgs.

Spray Coating

35 Kgs of the pan-coated low-density cores were loaded into a deseret-60fluid bed coater and fluidized. To this, 65.8 Kgs of a solutioncontaining 7.3% active alkaline protease and 2.1% polyvinylpyrolidine(Luviskol K-17 from BASF) was spray-coated onto the cores. Subsequently,a 40% solids solution containing 4.8 Kg of dry corn starch, 2.118 Kgs ofsucrose and 0.142 Kgs of hydrated starch was spray-coated onto theenzyme particulates. Finally, a cosmetic coating solution containing3.62 Kgs of hydroxymethyl cellulose (Methocel E from Dow chemical),4.352 Kgs of titanium dioxide and 0.731 Kgs of polyethylene glycol (PEG600) was spray-coated on as a final overcoating.

Spray coating Parameters: Outlet Fluidized Atomization Step Temperature(C.) Air Flow (CFM) Pressure (PSI) Core charge 50 1200 50 Enzyme spray55 1800 70 Sucrose/starch 45 1800 70 Cosmetic coat 65 1800 70

61.2 Kgs of final product was harvested. The volumetric densitydetermined by mineral oil immersion was 1.18 g/ml

Example 2

The following dry ingredients were blended in a Hobard mixer:

a) 600 grams of borosilicate hollowspheres (Q-cel 6042S)

b) 1050 grams of yellow dent corn starch

c) 600 grams of cellulose fibers (Arbosel 600-30)

d) 360 milligrams of lactose

e) 300 grams of high MW polyethylene glycol (PEG 3350 from Dow)

f) 36 grams of low MW polyethylene glycol (PEG 2200 from Dow)

g) 39 grams of polyvinylpyrolidine (Luviskol K-30 from BASF)

To this dry blend, 1615 grams of water was slowly blended in to producea suitable extrusion dough. The dough was then extruded into strandswith a 0.8 mm die. The extruded strands were then marumerized in orderto produce roughly spherical particulates.

695 grams of the low density marums were charged into a Vector FL-1fluidized bed spray-coater and fluidized with 65 CFM of 85° C.fluidizing air. To this, 1710 grams of a 17% w/w total solids solutioncontaining 25 grams of polyvinyl pyrolidine and 1685 grams of a liquidenzyme concentrate containing 7.4% alkaline protease was spray-coatedonto the low density marums. Subsequently, 1318 grams of a 25% w/w totalsolids solution containing 66 grams of lecithin (Ultralec-G from ADM)and 263 grams of yellow dent corn starch was spray coated onto theenzyme marum. Subsequently, 1520 grams of a 13% w/w total solidssolution including 82 grams of hydroxypropylmethyl cellulose (MethocelE-15), 99 grams of titanium dioxide and 17 grams of polyethylene glycol(PEG600) was overcoated onto the marums as a cosmetic coating.

1322 grams of product was recovered, with a volumetric density of 1.14g/ml as determined by mineral oil immersion

Example 3

The following dry ingredients were blended in a Hobard mixer:

a) 600 grams of borosilicate hollowspheres (Q-cel 6042S)

b) 1050 grams of yellow dent corn starch

c) 600 grams of cellulose fibers (Arbosel 600-30)

d) 360 milligrams of lactose

e) 300 grams of high MW polyethylene glycol (PEG 3350 from Dow)

f) 36 grams of low MW polyethylene glycol (PEG 2200 from Dow)

g) 39 grams of polyvinylpyrolidine (Luviskol K-30 from BASF)

To this dry blend, 2413 grams of a solution containing 11.4% alkalineprotease was slowly blended in to produce a suitable extrusion dough.The dough was then extruded into strands with a 0.8 mm die. The extrudedstrands were then marumerized in order to produce roughly sphericalparticulates.

952 grams of the low density enzyme marums were charged into a VectorFL-1 fluidized bed spray-coater and fluidized with 65 CFM of 85° C.fluidizing air. To this, 1318 grams of a 25% w/w total solids solutioncontaining 66 grams of lecithin (Ultralec-G from ADM) and 263 grams ofyellow dent corn starch was spray coated onto the enzyme marum.Subsequently, 1520 grams of a 13% w/w total solids solution including 74grams of hydroxypropylmethyl cellulose (Methocel E-15), 89 grams oftitanium dioxide, 20 grams of neodol 23/6.5 (Shell chemical) and 15grams of polyethylene glycol (PEG600) was overcoated onto the marums asa cosmetic coating.

1378 grams of product was recovered, with a volumetric density of 0.96g/ml as determined by mineral oil immersion.

Example 4

7.81 Kgs of sucrose seeds, sieved between 35 to 50 standard mesh, werecharged into a Glaft GPCG-30 fluidized bed coater, and fluidized with afluidizing air stream of warm air. To this, 126 Kgs of a 35% w/w totalsolids solution containing 35 Kgs of an enzyme solution containing 3718PU/gram alkaline protease, 32 Kgs of yellow dent corn starch, 56.2 Kgsof a solution containing 3.1 Kgs of “cooked out” yellow dent starch, 1.3Kgs of sucrose, 1.9 Kgs of borosilicate hollowspheres (Q-cel 6048) and76 grams of 98% formic acid was spray-coated onto the sucrose seeds.Subsequently, 56.3 Kgs of a 13% w/w total solids solution containing 3.3Kgs hydroxypropylmethyl cellulose (Methocel E-15), 3.3 Kgs titaniumdioxide and 0.7 Kgs of polyethylene glycol (PEG 600) was spray coatedonto the enzyme particulates as a cosmetic coating.

42.6 Kgs of product was recovered, with 95.7% of the product beinglarger than 600 um and smaller than 1.18 mm. The activity of the enzymeparticulates was 2314 PU/gram. Volumetric density determined by mineraloil immersion was 1.20 g/ml.

Example 6 Analysis of Granules

Stability

In terms of chemical (detergent) stability, granules of the presentinvention preferably exhibit no more than about 50% loss in activityover 4 weeks storage at 37° C. in detergent and cleaning agents (e.g.,dish detergents, laundry detergents, and hot surface cleaningsolutions). More preferably, the granules taught herein have a minimumof 70% activity remaining after 4 weeks at 37° C. More preferably still,the granules taught herein have a minimum of 85% activity remainingafter 4 weeks at 37° C. In tests carried out in support of the presentinvention, the granules of Example 1 exhibited nearly 85% activityremaining after 4 weeks at 37° C.

Dust Tests

Two commonly used methods for measuring enzyme granule dust are theHeubach attrition test and the elutriation test. These tests attempt toquantify the tendency of enzyme granules to generate airborne proteinaerosols which might potentiate allergic reactions among workers indetergent plants. These tests are designed to reproduce certainmechanical actions typical of handling, conveying and blendingoperations used to mix enzyme granules into detergents at commercialscale.

In the elutriation test, enzyme granules are placed on a glass fritwithin a tall glass tube, and fluidized with a constant dry air streamover a fixed time period. In the Heubach attrition test, granules areplaced in a small, cylindrical steel chamber fitted with a rotatingpaddle and steel balls; the granules are pushed around by the paddle andballs, while a dry air stream percolates up through the chamber. In bothtests, dust stripped from the particles by the air stream is captured ona glass fiber filter for subsequent weight measurement and activitydetermination. The elutriation test simulates the removal of surfacedust be gentle pouring and fluidizing actions; the Heubach test is amore severe simulation of the crushing forces commonly encountered inindustrial powder mixing, conveying, and sieving operations. Additionaldetails of these tests can be found, for example, in “Enzymes InDetergency,” ed. Jan H. van Ee, et al., Chpt. 15, pgs. 310-312 (MarcelDekker, Inc., New York, N.Y. (1997)), and references cited therein.

Granules of the present invention preferably exhibit a dust figure ofless than 1 ug/g (active dust) as determined by the elutriationattrition test. Exemplary granules that have been tested in support ofthe present invention exhibit a dust figure of no greater than 1 ug/g.

Enzyme Release

A commonly used method for measuring enzyme release from a granule undertypical liquid applications conditions is the enzyme dissolution test.In this test, granules are added to a liquor that is chemicallyequivalent to the application conditions. The test liquor can be set atdiffering temperatures to test for different application temperatures.The granule containing liquor is agitated under conditions that aresimilar to application conditions, and samples of particulate-freeliquor are removed with a filtered syringe at various times. The samplesare then assayed for enzyme activity (e.g., for proteases, by way of astandard assay involving the hydrolysis of casein substrate).

Granules of the present invention preferably have at least 80%, andpreferably at least 90%, of the enzyme activity released into the liquorwithin 5 minutes at 15° C. More preferably, the granules taught hereinhave a minimum of 90% of the enzyme activity released into the liquorwithin 3 minutes at 15° C. Exemplary granules that have been tested insupport of the present invention exhibit an enzyme release rate of noless than 90% in 5 minutes at 15° C, and most exhibit an enzyme releaserate of no less than 90% in 3 minutes at 15° C.

Summary Table Volumetric Granule Sample Density (g/ml) Example 1 1.18Example 2 1.14 Example 3 0.96 Exampie 4 1.20

Various other examples and modifications of the foregoing descriptionand examples will be apparent to a person skilled in the art afterreading the disclosure without departing from the spirit and scope ofthe invention, and it is intended that all such examples ormodifications be included within the scope of the appended claims. Allpublications and patents referenced herein are hereby incorporated byreference in their entirety.

It is claimed:
 1. A low-density composition including a non-porous orminimally porous, low-density material, a binder, and an enzyme, thecomposition having a specific gravity less than 1.2 g/cm³.
 2. Thecomposition of claim 1, wherein the non-porous or minimally porous,low-density material is selected from the group consisting ofhollowspheres, low-density minerals that are minimally soluble andminimally porous in water, low-density wood materials, and any mixturethereof.
 3. The composition of claim 2, wherein the non-porous orminimally porous, low-density material is comprised of hollowspheres. 4.The composition of claim 1, having a specific gravity of between 0.95and 1.15 g/cm³.
 5. An enzyme core for enzyme granules, comprising (i) alow-density composition including (a) a non-porous or minimally porous,low-density material and (b) a binder; and (ii) an enzyme enrobing saidcomposition, the enzyme core having a specific gravity less than 1.2g/cm³.
 6. The enzyme core of claim 5, wherein the non-porous orminimally porous, low-density material is selected from the groupconsisting of hollowspheres, low-density minerals that are minimallysoluble and minimally porous in water, low-density wood materials, andany mixture thereof.
 7. The enzyme core of claim 6, wherein thenon-porous or minimally porous, low-density material is comprised ofhollowspheres.
 8. The enzyme core of claim 5, wherein the low-densitycomposition is substantially free of enzymes therein.
 9. The enzyme coreof claim 5, having a specific gravity of between 0.95 and 1.15 g/cm³.10. The low-density composition of claim 1 further comprising an outercoating.
 11. The low-density composition of claim 10 wherein thenon-porous or minimally porous, low-density material is selected fromthe group consisting of hollowspheres, low-density minerals that areminimally soluble and minimally porous in water, low-density woodmaterials, and any mixture thereof.
 12. The low-density composition ofclaim 11 wherein the non-porous or minimally porous, low-densitymaterial is comprised of hollowspheres.
 13. The low-density compositionof claim 12 wherein the hollowspheres are borosilicate glasshollowspheres.
 14. The low-density composition of claim 10 having, aspecific gravity of 0.95 -1.15g/cm³.
 15. The enzyme core of claim 5further comprising an outer coating.
 16. The enzyme core of claim 15wherein the non-porous or minimally porous, low-density material isselected from the group consisting of hollowspheres, low-densityminerals that are minimally soluble and minimally porous in water,low-density wood materials, and any mixture thereof.
 17. The enzyme coreof claim 16 wherein the non-porous or minimally porous, low-densitymaterial is comprised of hollowspheres.
 18. The enzyme core of claim 17wherein the hollowspheres are borosilicate glass hollowspheres.
 19. Theenzyme core of claim 15 having a specific gravity of 0.95-1.15 g/cm³.